The model barbiturate dependency which we have developed in the cat will be used. Maximally tolerated daily barbiturate dosing for 5 weeks produces a quantitatively defined and reproducible dependency: 1. Withdrawal events will first be quantitated and correlated with blood barbiturate concentrations. 2. Intensities of withdrawal and dependency will be determined by correlation analysis of all neuropharmacologic events, pharmacokinetic data and dosing. 3. Dependencies produced by short and long acting barbiturates will be compared. This has never been done, although it is generally believed that severe withdrawal occurs with rapidly eliminated barbiturates. To do this properly requires (a) equieffective treatments throughout; (b) definition of elimination rates as withdrawal determinanats; (c) definition of the efficacy of different barbiturates to cause dependency. 4. The model dependency will provide a rational basis treatment evaluation. Phenobarbital treatment of withdrawal will be studied because its slow elimination should retard the exposure of dependent neurons. Diphenylhydantoin (DPH) will be studied; its status in the treatment of barbiturate and alcohol withdrawal is unsettled. Since withdrawal seizures may arise from a subcortical focus, trimethadione (TMD) merits study. TMD treatment of withdrawal has not been studied. 5. Since presynaptic endings are a key site of barbiturate action, events in intramedullary endings during withdrawal will be monitored pre-and post-synaptically by focal and intracellular recordings.